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15 september 2020: Bron: . 2020 Aug; 12(8): 2313. Published online 2020 Aug 17

Omdat nieuwe kankermedicijnen in Europa veel later op de markt komen dan in de Verenigde Staten gaan veel levensjaren verloren omdat kankerpatiënten voortijdig overlijden en zij niet de beste mogelijke behandeling krijgen. De vertraagde goedkeuring (gemiddeld 8 maanden voor Nederland in vergelijking met Amerika) zou ertoe leiden dat mensen in Europa, waaronder dus ook Nederland, eerder en onnodig komen te overlijden. In Oost-Europa is het verschil nog groter. Dit blijkt uit een studie van prof. dr. Carin Uyl-de Groot, werkzaam aan de Erasmus Universiteit Rotterdam. 

Een nieuw kankermedicijn komt in Europa na gemiddeld 403 dagen op de markt. In de VS gebeurt dat al na gemiddeld 161 dagen. Europese kankerpatiënten moeten dus gemiddeld 242 dagen langer op levensreddende medicijnen wachten dan kankerpatiënten in de Amerika. De goedkeuring in Europa ligt in handen van de EMA, die in Amerika in handen van de FDA.

Naast dat de aanvraag vaak later wordt gedaan moeten Europese lidstaten het positieve advies van het EMA overnemen voordat een medicijn op de markt mag komen. In Nederland regelt het Zorginstituut Nederland dat. Gemiddeld duurt zo'n goedkeuring hier in Nederland 128 dagen nadat het EMA goedkeruing heeft verleend. In Duitsland gemiddeld zeventien dagen. In Engeland (het Verenigd Koninkrijk) gemiddeld 22 dagen en in Oostenrijk gemiddeld 31 dagen. In Griekenland en Oost-Europese landen als Roemenië, Hongarije bv duurt dat vaak jaren of soms helemaal niet. 

Prof dr. Uyl-de Groot stelt dat de vertraging bij het goedkeuren van medicijnen tegen bv. melanomen (ipilimumab) en prostaatkanker (abiratereone) alleen al tot een verlies van 30.000 levensjaren in Europa heeft geleid. In Nederland zouden hierdoor al bijna dertienhonderd levensjaren verloren zijn gegaan.

Zij onderzocht 12 medicijnen die afgelopen 10 jaar bewezen hebben voor soms jarenlange levensverlenging te kunnen zorgen bij verschillende vormen van kanker. 

Table 1 en Appendix A tonen de data van de indiening bij en goedkeuring door de EMA en FDA.

Table 1

Newly registered oncological drugs, first indications, clinical values, and duration of EMA and FDA procedures.

DrugFirst IndicationGain PFS, OS, TTP (Median, Months)ESMO-MCBS *Date of EMA SubmissionDate of EMA ApprovalAccelerated Assessment (EMA)Total Time EMA (in Days)Date of FDA SubmissionDate of FDA ApprovalPriority Review (FDA)Total Time FDA (in Days)Time between EMA and FDA Approval (in Days)
Abiraterone Prostate cancer 3.9 months OS 4 17 December 2010 5 September 2011 16 December 2010 262 20 December 2010 28 April 2011 Yes 129 130
Cabazitaxel Prostate cancer 2.4 months TTP 2 20 April 2010 17 March 2011 n.a. 331 31 March 2010 17 June 2010 Yes 78 273
Dabrafenib Melanoma 2.4 months PFS 4 24 July 2012 26 August 2013 n.a. 398 30 July 2012 29 May 2013 No 303 89
Ipilimumab Melanoma 3.7 months OS 4 05 May 2010 12 July 2011 n.a. 433 10 June 2010 15 March 2011 No 278 119
Nivolumab Melanoma 4.0 months PFS 4 02 September 2014 19 June 2015 24 July 2014 290 30 July 2014 22 December 2014 No 145 179
Vemurafenib Melanoma 3.7 months PFS 4 04 May 2011 17 February 2012 14 April 2011 289 28 April 2011 17 August 2011 Yes 111 184
Pertuzumab Breast cancer 6.1 months PFS 4 01 December 2011 4 March 2013 n.a. 459 06 December 2011 08 June 2012 No 185 269
Enzalutamide Prostate cancer 4.8 months OS 4 26 June 2012 21 June 2013 n.a. 360 22 May 2012 31 August 2012 Yes 101 294
Pembrolizumab Melanoma 1.3 months PFS 3 04 June 2014 17 July 2015 n.a. 408 27 February 2014 03 September 2014 No 188 317
Ramucirumab Gastric cancer 2.2 months OS 2 23 August 2013 19 December 2014 n.a. 483 23 August 2013 21 April 2014 No 241 242
Palbociclib Breast cancer 10.3 months PFS 3 30 July 2015 9 November 2016 n.a. 468 30 June 2014 03 February 2015 Yes 218 645
Ribociclib Breast cancer PFS not reached 3 05 September 2016 22 August 2017 n.a. 351 29 August 2016 13 March 2017 Yes 196 162
Average time (in days) 378 181 242
Average time accelerated assessment/priority review (in days) 280 139 n.a.
Average time in case no accelerated assessment/no priority review (in days) 410 223 n.a.

* Ref. [] PFS: progression-free survival; OS: overall survival; TTP: time to progression, ESMO-MCBS: European Society Medical Oncology-Magnitude of Clinical Benefit Scale; EMA: European Medicines Agency; FDA: USA Food and Drug Association; n.a.: not applicable.

In Figure 2, wordt het EMA-traject per bestudeerd geneesmiddel gepresenteerd.

Figure 3 en Appendix B geven de gemiddelde tijd weer tussen de EMA-registratie en de eerste opname van de bestudeerde geneesmiddelen in Europa. 2-8 jaar na goedkeuring op de markt hadden verschillende landen nog steeds een zeer lage of helemaal geen opname van medicijnen. 
Palbociclib had de snelste time-to-market van EMA-registratie tot eerste opname in de EG (gemiddeld: 165 dagen), gevolgd door nivolumab (gemiddeld: 210 dagen), maar 2 jaar na goedkeuring op de Europese markt werden deze geneesmiddelen nog steeds niet voorgeschreven aan patiënten in respectievelijk vier en vijf landen. 
Merk op dat, ondanks de relatief snelle opname van palbociclib, de tijd tussen de markttoegang tot de VS en de EU bijna twee jaar bedroeg. Voor nivolumab was deze periode korter, namelijk 179 dagen.

Het volledige studierapport is gratis in te zien of te downloaden:

Abstract

Background. Many new cancer medicines have been developed that can improve patients’ outcomes. However, access to these agents comes later in Europe than in the United States (US). The aim of this study is to assess the access in Europe to newly registered cancer drugs and to get more insight in the implications of these variations for patients. Methods. A retrospective database study was conducted. Analyses involved 12 cancer drugs and 28 European countries in the period 2011–2018. Time to patient access, speed of drug uptake, and the potential loss of life years due to a delay in access have been studied. Results. Marketing approval for the cancer drugs came on average 242 days later in Europe than in the US, and actual patient access varied extensively across Europe. The average time to market in Europe was 403 days (range 17–1187 days). The delay in patient access of ipilimumab and abiraterone may have led to a potential loss of more than 30,000 life years. Conclusion. It takes a long time for patients to get access to newly registered cancer drugs and there is great variation in access. The health outcomes can be substantially improved by faster processes.

5. Conclusions

This study shows that it takes a long time for European patients to get access to newly registered cancer drugs. Further, there is great inter-country variation of access to new cancer drugs. The delay in access may result in a potential loss of many life years. The health outcomes of European patients can substantially be improved by enabling faster and more general use of available new medicines.

Author Contributions

C.A.U.-d.G. and R.H.: substantial contributions to the design and analysis of the work; C.A.U.-d.G., R.H., M.K., J.V.: substantial contribution to interpretation of data for the work; C.A.U.-d.G.: drafting the work; all authors: revising the work critical; all authors: final approval of the version to be published; all authors: agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All authors have read and agreed to the published version of the manuscript.

Funding

This work was supported by the “Vereniging Innovatieve Geneesmiddelen” (VIG), The Netherlands with an unrestricted grant.

Conflicts of Interest

C.A. Uyl-de Groot: Unrestricted grants from Boehringer Ingelheim, Astellas, Celgene, Sanofi, Janssen-Cilag, Bayer, Amgen, Genzyme, Merck, Gilead, Novartis, Astra Zeneca and Roche outside the submitted work. R. Heine: none. M. Krol: none. J. Verweij: Non-executive medical director: Octimet. Stock options: Octimet. Honoraria for consulting in last 24 months: Basilea, Genmab, InteRNA, Octimet, CoBioRes.

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Articles from Cancers are provided here courtesy of Multidisciplinary Digital Publishing Institute (MDPI)

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